A yeast BH3-only protein mediates the mitochondrial pathway of apoptosis

Sabrina Büttner, Doris Ruli, F. Nora Vögtle, Lorenzo Galluzzi, Barbara Moitzi, Tobias Eisenberg, Oliver Kepp, Lukas Habernig, Didac Carmona-Gutierrez, Patrick Rockenfeller, Peter Laun, Michael Breitenbach, Chamel Khoury, Kai Uwe Fröhlich, Gerald Rechberger, Chris Meisinger, Guido Kroemer, Frank Madeo

    Résultats de recherche: Contribution à un journalArticleRevue par des pairs

    116 Citations (Scopus)

    Résumé

    Mitochondrial outer membrane permeabilization is a watershed event in the process of apoptosis, which is tightly regulated by a series of pro-and anti-apoptotic proteins belonging to the BCL-2 family, each characteristically possessing a BCL-2 homology domain 3 (BH3). Here, we identify a yeast protein (Ybh3p) that interacts with BCL-X L and harbours a functional BH3 domain. Upon lethal insult, Ybh3p translocates to mitochondria and triggers BH3 domain-dependent apoptosis. Ybh3p induces cell death and disruption of the mitochondrial transmembrane potential via the mitochondrial phosphate carrier Mir1p. Deletion of Mir1p and depletion of its human orthologue (SLC25A3/PHC) abolish stress-induced mitochondrial targeting of Ybh3p in yeast and that of BAX in human cells, respectively. Yeast cells lacking YBH3 display prolonged chronological and replicative lifespans and resistance to apoptosis induction. Thus, the yeast genome encodes a functional BH3 domain that induces cell death through phylogenetically conserved mechanisms.

    langue originaleAnglais
    Pages (de - à)2779-2792
    Nombre de pages14
    journalEMBO Journal
    Volume30
    Numéro de publication14
    Les DOIs
    étatPublié - 20 juil. 2011

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